Alternating hemiplegia of childhood: episodes of paralysis that vanish in sleep

In alternating hemiplegia of childhood, paralysis comes and goes, sometimes switching sides of the body, and every symptom disappears during sleep. MedlinePlus Genetics, from the National Library of Medicine, describes this rare neurological condition and its genetics.

The episodes

The condition is marked by recurrent episodes of temporary paralysis, often on one side of the body (hemiplegia). In some episodes the paralysis moves from one side to the other, or affects both sides at once. They begin in infancy or early childhood, usually before 18 months of age, and each lasts from minutes to days.

Other attacks can come with the paralysis or on their own: sudden uncontrollable muscle activity, including involuntary limb movements (choreoathetosis), muscle tensing (dystonia), eye movements (nystagmus) or shortness of breath (dyspnea). The skin may suddenly flush red and warm, or turn unusually pale.

Episodes can be set off by stress, extreme tiredness, cold temperatures or bathing, though the trigger is not always known. A characteristic feature is that all symptoms disappear during sleep, although they can return shortly after waking. Through childhood the number and length of episodes grow worse, then begin to decrease. The uncontrollable movements may vanish entirely, but the episodes of hemiplegia continue throughout life.

The condition also causes cognitive problems, mild to severe. Almost everyone affected has some developmental delay and intellectual disability, and cognitive functioning typically declines over time.

How common

It is rare, affecting approximately 1 in 1 million people.

Causes

The two genes give instructions for very similar proteins, which serve as different forms of the alpha subunit of a larger protein complex called Na+/K+ ATPase. The two versions of the complex are found in different parts of the brain, and both are critical to the normal function of nerve cells (neurons). Na+/K+ ATPase moves charged atoms (ions) into and out of neurons, an essential part of the signaling that controls muscle movement.

Mutations in either gene reduce the activity of the complex and impair its ability to transport ions normally. It is unclear how a malfunctioning Na+/K+ ATPase leads to the episodes of paralysis or uncontrollable movements.

Inheritance

The condition is considered autosomal dominant, meaning one altered copy of the gene in each cell is enough to cause the disorder. Most cases result from new mutations and occur in people with no family history, but the condition can also run in families. For unknown reasons, signs and symptoms are typically milder when several family members are affected than when one person is.

Autosomal dominant inheritance with a new (de novo) mutation. U.S. National Library of Medicine.

Autosomal dominant inheritance. U.S. National Library of Medicine.

The condition is also known as alternating hemiplegia syndrome.

Sources

• MedlinePlus Genetics, National Library of Medicine, Alternating hemiplegia of childhood; rewritten in hubnx's own words.